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Evolving reversible iMmunocapture by membrane sensing peptides: towARds scalable extracellular VEsicLes isolation

Project description

Upscaling extracellular vesicles for biomedical use

The extracellular vesicles (EV) released by cells as part of cell-to-cell communication are being considered for therapeutic and diagnostic purposes. The aim of the EU-funded MARVEL project is to overcome bottlenecks in EV isolation to scale up the process beyond the analytical. For this purpose, scientists will employ a new technology for reversible isolation originally developed during the H2020 INDEX project that will be implemented with membrane-sensing peptides. This will represent a paradigm shift from antibodies to peptides as an alternative class of affinity ligands characterised by high efficiency of EV capturing. The technology will be applied to the development of EV-based medicinal products for cardiac repair and to the diagnosis of bladder cancer in urine samples.

Objective

Extracellular vesicles (EV) are submicron membrane vesicles released by most cells with a fundamental role in cell-to-cell communication. Much interest is flourishing towards their exploitation in regenerative medicine and diagnostics. However, the fulfilment of the EV promise is hampered by severe limitations in their isolation, characterization and manufacturing. A particularly arduous task is to move the isolation of specific EV subpopulations beyond the analytical scale and towards scalable processes. In this scenario, our project will leverage on DNA-directed reversible immunocapturing (rDDI), a new technology developed within FET-OPEN project “INDEX”. rDDI relies on the reversible EV isolation mediated by immunoaffinity followed by intact vesicles recovery upon enzymatic cleavage of a DNA linker used to anchor antibodies on solid supports. Despite unprecedented efficiency in the recovery of highly pure EVs, limitations inherent to antibodies (high costs, batch-to-batch variation and limited versatility of chemical manipulation) substantially impair the scalability of rDDI for any operating scale exceeding the analytical one. MARVEL targets a paradigm shift from antibodies to peptides as an alternative class of affinity ligands for EV capturing by introducing membrane-sensing peptides (MSP) as novel ligands for the size-selective capturing of small EV, unbiased by differential surface protein expression. MARVEL mission is to combine and implement rDDI and MSP technologies, towards the first and best performing ever affinity-based technology for scalable and reversible small EV (<200nm) isolation. The modularity in scaling-up of the novel protocols and kits will be demonstrated on medium/large sample volumes in relevant environments for therapeutic and diagnostics use of EVs and specifically: 1) In the manufacturing of GMP-grade EVs as a medicinal product for cardiac repair; 2) In urine-based liquid biopsy for bladder cancer diagnostics.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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RIA - Research and Innovation action

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-FETPROACT-2019-2020

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Coordinator

CONSIGLIO NAZIONALE DELLE RICERCHE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 773 158,75
Address
PIAZZALE ALDO MORO 7
00185 Roma
Italy

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Region
Centro (IT) Lazio Roma
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 773 158,75

Participants (6)

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